SNARE complex polymorphisms associate with alterations of visual selective attention in Alzheimer's disease

Research output: Contribution to journalArticle

Abstract

The SNARE complex plays a crucial role in the synaptic exocytosis of neurotransmitters, a process involved in the Alzheimer's disease (AD), the most common form of dementia. SNAP-25, STX1a, and VAMP2 are the core proteins of the SNARE complex, and changes in protein level are suggested to contribute to cognitive impairment and neuropsychiatric disorders. Single nucleotide polymorphisms (SNPs) in SNARE complex genes were shown to be associated with different diseases and different cognitive impairments. Chi-square analysis was used to compare case-control difference of ApoE4, SNAP-25 rs363039, rs363043, rs363950, STX1a rs4717806, rs2293489, and VAMP2 26bp Ins/Del genotype distribution in 192 AD, 187 mild cognitive impairment (MCI), and 200 healthy controls (HC). Results of genotype and allelic distribution of SNAP-25 rs363050 showed that AA genotype (AD versus HC: p=1.5×10 -4; MCI versus HC: p=8.7×10 -3) as well as A allele (AD versus HC: p=6.0×10 -4; MCI versus HC: p=5.7×10 -3) are significantly more frequent in AD and MCI compared to HC. Genotype distribution of STX1a rs4717806 and rs2293489 resulted significantly different in AD compared to HC (p=0.032 and p=0.047, respectively). Moreover, distribution of the STX1a rs4717806 allele in SNAP-25 rs363050 AA carriers was significantly different between MCI and HC (p=0.018). Notably, in MCI, visual selective attention impairment was associated with the STX1a rs4717806 AA (p c =0.027) genotype as well as the SNAP-25/STX1a rs363050/rs4717806 AA/A (p c =0.022) combination. These data suggest that SNPs in SNARE complex genes may interfere and/or modulate the activity of the SNARE complex resulting in impairments of neurotransmission that involve attention brain areas.

Original languageEnglish
Pages (from-to)179-188
Number of pages10
JournalJournal of Alzheimer's Disease
Volume69
Issue number1
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

SNARE Proteins
Alzheimer Disease
Genotype
Vesicle-Associated Membrane Protein 2
Single Nucleotide Polymorphism
Alleles
Apolipoprotein E4
Cognitive Dysfunction
Exocytosis
Synaptic Transmission
Genes
Neurotransmitter Agents
Dementia
Brain

Keywords

  • Alzheimer's disease
  • cognitive impairment
  • gene polymorphisms
  • mild cognitive impairment
  • SNAP-25
  • SNARE
  • SNPs
  • STX1a
  • VAMP2

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

@article{3fcdea4852894f4d9a2cb45a39cfc83c,
title = "SNARE complex polymorphisms associate with alterations of visual selective attention in Alzheimer's disease",
abstract = "The SNARE complex plays a crucial role in the synaptic exocytosis of neurotransmitters, a process involved in the Alzheimer's disease (AD), the most common form of dementia. SNAP-25, STX1a, and VAMP2 are the core proteins of the SNARE complex, and changes in protein level are suggested to contribute to cognitive impairment and neuropsychiatric disorders. Single nucleotide polymorphisms (SNPs) in SNARE complex genes were shown to be associated with different diseases and different cognitive impairments. Chi-square analysis was used to compare case-control difference of ApoE4, SNAP-25 rs363039, rs363043, rs363950, STX1a rs4717806, rs2293489, and VAMP2 26bp Ins/Del genotype distribution in 192 AD, 187 mild cognitive impairment (MCI), and 200 healthy controls (HC). Results of genotype and allelic distribution of SNAP-25 rs363050 showed that AA genotype (AD versus HC: p=1.5×10 -4; MCI versus HC: p=8.7×10 -3) as well as A allele (AD versus HC: p=6.0×10 -4; MCI versus HC: p=5.7×10 -3) are significantly more frequent in AD and MCI compared to HC. Genotype distribution of STX1a rs4717806 and rs2293489 resulted significantly different in AD compared to HC (p=0.032 and p=0.047, respectively). Moreover, distribution of the STX1a rs4717806 allele in SNAP-25 rs363050 AA carriers was significantly different between MCI and HC (p=0.018). Notably, in MCI, visual selective attention impairment was associated with the STX1a rs4717806 AA (p c =0.027) genotype as well as the SNAP-25/STX1a rs363050/rs4717806 AA/A (p c =0.022) combination. These data suggest that SNPs in SNARE complex genes may interfere and/or modulate the activity of the SNARE complex resulting in impairments of neurotransmission that involve attention brain areas.",
keywords = "Alzheimer's disease, cognitive impairment, gene polymorphisms, mild cognitive impairment, SNAP-25, SNARE, SNPs, STX1a, VAMP2",
author = "Costa, {Andrea Saul} and Guerini, {Franca Rosa} and Beatrice Arosio and Daniela Galimberti and Milena Zanzottera and Anna Bianchi and Raffaello Nemni and Mario Clerici",
year = "2019",
month = "1",
day = "1",
doi = "10.3233/JAD-190147",
language = "English",
volume = "69",
pages = "179--188",
journal = "Journal of Alzheimer's Disease",
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TY - JOUR

T1 - SNARE complex polymorphisms associate with alterations of visual selective attention in Alzheimer's disease

AU - Costa, Andrea Saul

AU - Guerini, Franca Rosa

AU - Arosio, Beatrice

AU - Galimberti, Daniela

AU - Zanzottera, Milena

AU - Bianchi, Anna

AU - Nemni, Raffaello

AU - Clerici, Mario

PY - 2019/1/1

Y1 - 2019/1/1

N2 - The SNARE complex plays a crucial role in the synaptic exocytosis of neurotransmitters, a process involved in the Alzheimer's disease (AD), the most common form of dementia. SNAP-25, STX1a, and VAMP2 are the core proteins of the SNARE complex, and changes in protein level are suggested to contribute to cognitive impairment and neuropsychiatric disorders. Single nucleotide polymorphisms (SNPs) in SNARE complex genes were shown to be associated with different diseases and different cognitive impairments. Chi-square analysis was used to compare case-control difference of ApoE4, SNAP-25 rs363039, rs363043, rs363950, STX1a rs4717806, rs2293489, and VAMP2 26bp Ins/Del genotype distribution in 192 AD, 187 mild cognitive impairment (MCI), and 200 healthy controls (HC). Results of genotype and allelic distribution of SNAP-25 rs363050 showed that AA genotype (AD versus HC: p=1.5×10 -4; MCI versus HC: p=8.7×10 -3) as well as A allele (AD versus HC: p=6.0×10 -4; MCI versus HC: p=5.7×10 -3) are significantly more frequent in AD and MCI compared to HC. Genotype distribution of STX1a rs4717806 and rs2293489 resulted significantly different in AD compared to HC (p=0.032 and p=0.047, respectively). Moreover, distribution of the STX1a rs4717806 allele in SNAP-25 rs363050 AA carriers was significantly different between MCI and HC (p=0.018). Notably, in MCI, visual selective attention impairment was associated with the STX1a rs4717806 AA (p c =0.027) genotype as well as the SNAP-25/STX1a rs363050/rs4717806 AA/A (p c =0.022) combination. These data suggest that SNPs in SNARE complex genes may interfere and/or modulate the activity of the SNARE complex resulting in impairments of neurotransmission that involve attention brain areas.

AB - The SNARE complex plays a crucial role in the synaptic exocytosis of neurotransmitters, a process involved in the Alzheimer's disease (AD), the most common form of dementia. SNAP-25, STX1a, and VAMP2 are the core proteins of the SNARE complex, and changes in protein level are suggested to contribute to cognitive impairment and neuropsychiatric disorders. Single nucleotide polymorphisms (SNPs) in SNARE complex genes were shown to be associated with different diseases and different cognitive impairments. Chi-square analysis was used to compare case-control difference of ApoE4, SNAP-25 rs363039, rs363043, rs363950, STX1a rs4717806, rs2293489, and VAMP2 26bp Ins/Del genotype distribution in 192 AD, 187 mild cognitive impairment (MCI), and 200 healthy controls (HC). Results of genotype and allelic distribution of SNAP-25 rs363050 showed that AA genotype (AD versus HC: p=1.5×10 -4; MCI versus HC: p=8.7×10 -3) as well as A allele (AD versus HC: p=6.0×10 -4; MCI versus HC: p=5.7×10 -3) are significantly more frequent in AD and MCI compared to HC. Genotype distribution of STX1a rs4717806 and rs2293489 resulted significantly different in AD compared to HC (p=0.032 and p=0.047, respectively). Moreover, distribution of the STX1a rs4717806 allele in SNAP-25 rs363050 AA carriers was significantly different between MCI and HC (p=0.018). Notably, in MCI, visual selective attention impairment was associated with the STX1a rs4717806 AA (p c =0.027) genotype as well as the SNAP-25/STX1a rs363050/rs4717806 AA/A (p c =0.022) combination. These data suggest that SNPs in SNARE complex genes may interfere and/or modulate the activity of the SNARE complex resulting in impairments of neurotransmission that involve attention brain areas.

KW - Alzheimer's disease

KW - cognitive impairment

KW - gene polymorphisms

KW - mild cognitive impairment

KW - SNAP-25

KW - SNARE

KW - SNPs

KW - STX1a

KW - VAMP2

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DO - 10.3233/JAD-190147

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VL - 69

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JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

SN - 1387-2877

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